H. Lee Moffitt Cancer Center & Research Institute

Current Concepts in the Management of Tumors of the Skull Base

Akio Morita, MD, Laligam N. Sekhar, MD, and Donald C. Wright, MD


Approaches to the management of cranial base tumors, including surgery, radiotherapy, chemotherapy, hormonal therapy, and combinations of therapy, are individually tailored according to anatomy, tumor classification, and biologic aggressiveness.


Background:  Due to their involvement with critical neurovascular structures, tumors located in the cranial base present challenges to neurosurgeons and are associated with high morbidity and mortality.
Methods:  Rates of tumor control, complications, patient outcomes, and recurrences were extracted and summarized from two decades of our surgical and radiological treatment follow-up and review of the medical literature.
Results:  Recent advances in surgical techniques involving cranial base approaches have made surgical intervention safer and curative resection more likely.  In managing benign tumors, surgical resection is the gold standard for treatment.  While immediate complications are still significant, long-term outcomes in most cases are excellent.  Focused radiosurgery using a gamma knife or linear accelerator has produced favorable outcomes, and it improves the management of small or minimally symptomatic cranial base tumors.  For slow-growing malignant tumors, extensive surgery followed by radiotherapy achieves the best outcome.  In managing highly malignant tumors, outcome is determined by the effects of chemotherapy and radiotherapy.  On some occasions, surgery is needed to obtain greater control of highly malignant tumors.
Conclusions:  Skull base tumors are relatively common, and management of these tumors is rapidly evolving.  The combination of surgical excision using cranial base techniques, radiosurgery, fractionated radiotherapy, and chemotherapy should be individually tailored based on the location and pathological aggressiveness of the tumor and the symptomatology of the patient.


Introduction

    Management of tumors in the cranial base has been challenging for neurosurgeons and other medical specialists for more than a century.1 Since tumors are located deep in the skull and can involve important neurovascular structures, surgical treatment was associated with high morbidity and mortality. Until recently, radiation therapy was the standard palliative measure. However, during the 1970s and 1980s, neurosurgeons and head and neck surgeons2-4 introduced advances in surgical instrumentation and developed new approaches to the cranial base. Simultaneously, focused stereotactic radiotherapy was introduced to treat localized tumors in a more refined manner.5 With this combination of modern techniques, recent management of skull base tumors has dramatically improved.6

General Concepts

Classification and Management

    Various types of tumors involve the skull base. As depicted in Table 1, the most frequent types of tumors treated in our institutions are meningiomas, pituitary adenomas, and schwannomas. However, the numbers can be significantly influenced on a referral basis. In general, we can classify and discuss the management of the cranial base tumors according to their individual histopathologic types. Since there are numerous types of tumors, we have limited their classifications to three groups based on biologic aggressiveness, and in nine territories based on their location. This classification system not only simplifies our choice of treatment modalities, but also clarifies our understanding of the pathophysiology in clinical presentation. Biologic aggressiveness directs our decision on which mode of treatment is the best from an oncological standpoint, and the location of tumor and clinical presentation provide information on the risks that are involved in treatment.

Table 1. -- Cranial Base Tumors Treated at The George Washington University Medical Center (1993 to August 1997) 

Types of Skull Base Tumors Numbers of Cases
 
Meningiomas 356
Pituitary adenomas 133
Schwannomas 94
Chordomas 37
Chondrosarcomas 19
Craniopharyngiomas 14
Glomus jugulare tumors 14
Epidermoid cysts 13
Cholesterol granulomas 10
Fibrous dysplasia 8
Hemangiomas in cavernous sinus 7
Other benign tumors  6
Carcinomas of the skull base 19
Other malignant tumors 4
 
Total 734

Biologic Aggressiveness

    We group skull base tumors in roughly three pathologic entities: benign, slow-growing (low-grade), and fast-growing (high-grade) malignancies. Table 2 shows examples of each category.

Table 2. -- Classification of Histologic Types of Cranial Base Tumors 

Benign Tumors:
Meningiomas
Schwannomas
Pituitary adenomas
Paragangliomas
Hemangiomas in cavernous sinus
Epidermoid cysts
Juvenile angiofibromas
Fibrous dysplasia
Cholesterol granulomas
 
Intermediate Malignant Tumors (Low Grade, Slow Growing): 
 
Chordomas
Chondrosarcomas
Adenoid cystic carcinomas
Low-grade esthesioneuroblastomas
 
Highly Malignant Tumors (Fast Growing): 
 
Carcinomas (adenocarcinoma, squamous, transitional, undifferentiated)
Sarcomas (rhabdomyosarcoma, Ewing's sarcoma, fibrosarcomas)
Higher-grade esthesioneuroblastomas
Lymphomas
Myelomas
Metastasis

    Benign tumors grow in an expansive fashion and induce clinical symptoms by exerting pressure on certain neurovascular structures. Hence, the reduction of the mass effect and, if possible, the complete excision of tumors are the gold standard in treating such lesions. Usually, symptoms caused by the mass effect can resolve fairly quickly. However, there are always associated surgical risks that may depend significantly on the location and extent of the tumor. With the recent development of diagnostic techniques, asymptomatic or minimally symptomatic tumors are being discovered in the skull base. With benign tumors, treatment modalities should be chosen based on observation, the excision of the tumor by surgery, or the control of tumor growth by stereotactic or conventional radiotherapy. The long-term benefits and risks of each procedure and the natural history of various tumor should be carefully assessed.7,8

    Slow-growing malignancies such as chondrosarcomas, chordomas, low-grade esthesioneuroblastomas, and adenoid cystic carcinomas are best treated with a combined mode of surgical debulking and radiotherapy.9-11 Sensitivity to radiotherapy is variable with each tumor type. Surgical resection should be as complete as possible, especially with radioresistant tumors such as chordomas. Cranial base approaches are useful to facilitate such procedures because they provide the surgeon with an excellent view from which to remove tumors and involved bones. Radiotherapy can involve either fractionated or focused radiosurgery depending on the size and extent of the tumor. Focused heavy particle irradiation is reported with a favorable outcome in cases with chordomas and chondrosarcomas.12

    Highly malignant tumors can be removed en bloc if the process does not involve critical structures. However, in most situations, piecemeal resection or sacrifice of a significant structure may be involved in surgical resection. Hence, radiotherapy with or without chemotherapy is the main treatment modality when the cranial base approach to a tumor may cause the loss of sensitive cranial structures.

Tumor Location

    Tumor location significantly affects our surgical strategy. Table 3 summarizes the classification of location, the frequently encountered tumors in each site, and the involved neurovascular structures and symptoms. The tumor’s relation to adjacent structures such as the optic apparatus should be considered. Tumors involved in more than one territory can present more complex problems. Because of the complexity in anatomical structures, the cavernous sinus (parasellar) and the petroclival areas are the most frequently discussed territory for the management of the skull base tumors.

Table 3. -- Skull Base Territories, Common Tumors, Involved Structures, and Clinical Presentation 

Skull Base Territory Common Tumors Involved Structures and Clinical Presentation
 
Anterior Cranial Base
 
  Central Meningioma Olfactory nerve
  Encephalocele Frontal lobe dysfunction (personality change)
  Nasal paranasal carcinoma Increased intracranial pressure
  Esthesioneuroblastoma Vision changes
  Nasal discharge
  Obstruction
 
  Lateral Fibrous dysplasia Orbit
  Vision changes
  Superior orbital fissure involvement
  Exophthalmos
 
Middle Cranial Base
 
  Central Pituitary adenoma Pituitary
  Meningioma Hypothalamus (hormonal changes, diabetes insipidus)
  Craniopharyngioma Optic nerve
  Sphenoid cancer Chiasm
  Mucocele
 
  Paracentral (cavernous) Meningioma Optic nerve in apex
  Schwannoma Cranial nerve 3-6
  Cavernous hemangioma Temporal and frontal lobe
  Chordomas Cavernous carotid artery
  Facial pain
  Diplopia
 
  Lateral Meningiomas Trigeminal divisions
  Schwannoma Lateral orbit
  Juvenile angiofibroma Infratemporal fossa
  Adenoid cystic carcinoma
 
Posterior Cranial Base
 
  Upper central (petroclival-clival) Meningioma 5th and 6th nerve
  Schwannoma CN 3, 4, 7, 8, 9 (10th if progress)
  Epidermoid Pons
  Chordoma Cerebellum and hydrocephalus
  Chondrosarcoma Carotid
  Cholesterol granuloma Basilar artery
  Cholesteatoma
 
  Lower central (foramen magnum) Meningioma 11th, 12th nerve
  Schwannoma Lower cranial nerves if progress
  Chordoma Various degree of sensorimotor long-tract sign (weakness, stereoagnosis, cape shape anesthesia in neck, dysesthesia and atrophy of hand)
 
  Upper lateral (CP angle) Schwannoma 7th and 8th nerve (often involved)
  Meningioma 5th and lower cranial nerves
  Lipoma Pons and cerebellum
  Epidermoid
 
  Lower lateral (jugular foramen) Schwannoma 9th-11th nerve
  Paraganglioma 12th nerve (if involving retropharyngeal space or occipital condyle)
  7th/8th nerve in EP angle or temporal bone
  Tinnitus
  Dysphagia

Diagnostic Studies and Interventional Radiological Treatment

    Diagnostic studies for skull base tumors include magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), computed tomography (CT) scans, bone window and three-dimensional (3-D) CT scans, and angiography. MRI is currently an essential test to show the nature and extent of the tumor. Tumor appearance on T1- and T2-weighted images a